Drug – bio-affecting and body treating compositions – Lymphokine – Interferon
Reexamination Certificate
1999-07-20
2002-02-26
Eyler, Yvonne (Department: 1646)
Drug, bio-affecting and body treating compositions
Lymphokine
Interferon
C424S085400, C435S069510, C514S002600
Reexamination Certificate
active
06350443
ABSTRACT:
TECHNICAL FIELD
The present invention relates to a method of treatment for feline leukemia virus infections. Being an RNA tumor virus, which is a retrovirus, the feline leukemia virus is integrated into the DNA of its host cell. Due to infection by feline leukemia viruses, a great many types of hematopoietic diseases may develop. Specific hematopoietic diseases include, for example, immune system suppression, lymphatic leukemia, and sarcomas in lymphatic cells; agranulocytosis such as neutropenia, anemia, thrombocytopenia, and leukemia in bone marrow cells; and chronic stomatitis as complications with bacterial infection. In latter stages after infection with feline leukemia viruses, anemia and chronic stomatitis are often clinically observed, and the development of effective therapeutic agents and methods of treatment therefor has been eagerly awaited. However, although it will take many years before development of serious diseases, as described above, after infection with feline leukemia viruses, in the early stages after infection with these viruses, elevation of body temperature associated with a decrease in the number of neutrophils, decreases in vigor and appetite, and aggravation of other general clinical symptoms are often observed. Aggravation of neutropenia may sometimes result in death.
BACKGROUND ART
Conventionally, methods of treatment for feline leukemia virus infections mainly include symptomatic therapies using steroid hormones. Although human erythropoietin has been experimentally used as a remedy for anemia, satisfactory effects have not yet been achieved.
As causal therapies, use of synthetic anticancer agents which are human chemotherapeutics and use of a human &agr; (alpha)-interferon have been proposed; however, the effects thereof are not satisfactory.
Hoover, et al., at Colorado State University, have attempted experimental therapies using AZT (3′-azido-3′-deoxythymidine) and a human &agr;-interferon for an immunodeficiency syndrome due to a feline leukemia virus, and have reported a reduction effect on the p27 antigen, which is an antigen of the feline leukemia virus. However, they have also admitted that the effect diminishes because antibodies are produced against the human interferon, which is a foreign protein to cats, after continued administration of the human &agr;-interferon, and thus, there is a problem in this as a method of treatment for feline leukemia virus infections. [Zeidner, N. S., Myles, M. H., Mathiason, D. C., Dreit, M. J., Mullins, J. I. and Hoover, E. A.; 1990a; Alpha Interferon(2b) in combination with zidovudine for the treatment of presymptomatic feline leukemia virus-induced immunodeficiency syndrome; Antimicrob. Agents Chemother.; 34: 1749-1749.]
Tompkins, et al., at North Carolina State University, have reported that, as treatment for feline leukemia viral lymphoma development, DEC (diethylcarbamazine) and AZT are effective at reducing p27 antigen and at prolonging life. However, neither was effective for neutropenia. [Nelson, P., Sellon, R., Novotoney, C., Devera, C., Davidian, M., English, R., Tompkins, M., and Tompkins, W.; 1995; Vet. Immunol. Immunopathol.; 46,181-194]
Cummins, et al., have orally administered to cats infected with feline leukemia viruses a low dose of a human &agr;-interferon and have reported that it is effective at prolonging life, although there is no effect on virus antigens. Although this therapy was later globally investigated as a method for treating human AIDS, the use thereof has not been implemented. [Weiss, R. C., Cummins, J. M., and Richards, A. B.; 1991; JAVMA; 199,1477-1481]
In various feline leukemia virus infections, since, in many cases, immunocompetence of cats is believed to be degraded, heavy use of steroid hormones, which are immunosuppressant agents, is not desirable, and side effects thereof often present a problem.
In addition, use of synthetic anticancer agents which are human chemotherapeutics and the oral administration of a small amount of a human &agr;-interferon are not adequately effective, and in the former synthetic anticancer agents, in particular, side effects are a problem.
As a feline interferon, a recombinant feline &ohgr;-interferon preparation has already been approved as a therapeutic agent for feline calicivirus infection, and has been commercially available under the trade name “INTERCAT” since February 1994. The present inventors have achieved the present invention as a result of the investigation of a method of treatment for feline leukemia virus infection using the recombinant feline &ohgr;-interferon.
Currently interferons are known to be of the following types: alpha (&agr;), beta (&bgr;), gamma (&ggr;), omega (&ohgr;), and tau (&tgr;). Although use of three types &agr;, &bgr;, and &ggr;has been implemented with respect to human interferons, in feline interferons, use of the &ohgr;-type only has been implemented. “INTERCAT” is a recombinant feline &ohgr;-interferon preparation, and is an injectable preparation produced by a method including the steps of infecting a silkworm with a baculovirus having recombinant feline &ohgr;-interferon genes; extracting and purifying products of the body thereof; adding thereto gelatin and D-sorbitol as stabilizers and vehicles; and freeze-drying. The recombinant feline &ohgr;-interferon is a glycoprotein having a molecular weight of approximately 25,000, and the protein portion thereof has the amino acid sequence as shown in the sequence listing (SEQ ID:1).
The feline &ohgr;-interferon may be produced by other methods, in addition to the use of silkworms. For example, it may be produced by a transient expression method using zooblasts such as simian COS cells, or by gene recombination techniques using CHO cells of Chinese hamsters,
E. coli
, yeast, transgenic animals, or the like.
With respect to the administration/dosage of INTERCAT which has been approved as a therapeutic agent for feline calcivirus infectious diseases, 2.5 to 5 MU/kg of the feline interferon is required to be administered intravenously once a day for three times every other day. Herein, an MU (megaunit) represents a titer used as a measure of the antiviral activity of the interferon, and is equal to one million units. Although treatment for feline leukemia virus infections, in particular, neutropenia, was attempted by administering INTERCAT every other day with the same administration/dosage as those for the approved therapeutic agent for feline calicivirus infections, the anticipated effects were not obtained. Therefore, by changing the administration/dosage, further investigations were carried out.
DISCLOSURE OF INVENTION
It is an object of the present invention to provide a novel and superior method of treatment which is suitable for feline leukemia virus infections, and in particular, for neutropenia.
In order to achieve the object described above, the present inventors investigated and discovered a method of treatment for feline leukemia virus infections by administering to cats by injection a therapeutic agent containing a feline &ohgr; (omega)-interferon, leading to the present invention.
That is, the object of the present invention has been achieved with industrial advantages by the present invention comprising the following aspects.
(1) A method of treatment for feline leukemia virus infections including continuous daily administration of a feline interferon preparation containing a feline interferon as a main component to a cat.
(2) A method of treatment for feline leukemia virus infections according to (1), wherein the feline interferon is a feline &ohgr; (omega)-interferon.
(3) A method of treatment for feline leukemia virus infections according to (2), wherein the feline &ohgr;-interferon is a recombinant interferon.
(4) A method of treatment for feline leukemia virus infections according to (3), wherein the feline &ohgr;-interferon is an interferon having an amino acid sequence shown in the sequence number 1 in which a sugar chain is connected.
(5) A method of treatment for feline leukemia virus
Kajimoto Tsunesuke
Shimoda Tetsuya
Andres Janet L.
Eyler Yvonne
Schnader Harrison Segal & Lewis LLP
Toray Industries Inc.
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